1. Field of the Invention
This invention relates to the art of sample liquid analysis and, more particularly, to a new and improved analytical device for performing dry chemistry analysis of aqueous fluids. As used herein, dry chemistry analysis refers to analytical methods and techniques that are carried out using chemical reagents contained in various "dry-to-the-touch" test elements such as single layer or multilayer test elements and the like.
2. Description of the Prior Art
An increasingly large number of analytical tests, procedures and analysis, i.e., assays, must be performed each day on many kinds of liquid samples, including, but not limited to aqueous biological fluids such as blood, serum, urine, cerebrospinal fluid and the like. Various methods have been developed for conducting such analysis, including those known in the art as dry chemistry analysis techniques.
A prolific dry chemistry analytical element and one form most readily adaptable for use in automated sample liquid analysis systems is the multilayer test element. Traditional multilayer analysis techniques rely on film technology wherein reagents are applied to a transparent film supported in layers. Such multilayer devices, which are well known in the art, may consist of one or more spreading layers, reaction layers, separation layers and detection layers superimposed one on the other, according to the analyte to be detected and the method of analysis used. These multilayer analytical elements are typically custom designed to the particular assay to be performed. That is, there is generally no generic structure that can be adopted for such an analytical element, and the number of different analytes that can be detected using a multilayer element of a particular construction is limited.
Generally speaking, to perform an assay using a typical multilayer test element, a sample of body fluid is applied to a spreading layer to assure even distribution of the sample to an underlying reaction layer which may contain a reagent component. This liquid sample and first reagent mixture then passes into a second underlying layer for reaction with additional reagent components. Since the reagent containing layers may be in contact with each other the cross migration of their respective reagent components and hence the potential of unintentional contamination of each layer exists. Generally, devices so constructed do not allow for the performance of sequential operation. The liquid sample and liquid sample reagent mixture will flow from one layer to the contiguous layer unless a separate timing layer is provided therebetween. The timing layer retains for a certain period of time the liquid in the top layer until the reaction is substantially completed and then releases the resulting reaction product to diffuse into the underlying layer.
The desirability of maintaining the reagent containing layers in spaced relationship to each other to minimize contamination and to provide some control over the timing of the assay sequence has been recognized in the art. Multilayer analytical devices have been provided wherein a liquid test sample contacts a reagent in a first reagent layer, with this layer adapted to thereafter be brought into contact with a second layer by moving the first and second layers into fluid contact with each other when a certain stage in the reaction is reached. See, for example, U.S. Pat. Nos. 4,258,001 and 4,357,363, both assigned to Eastman Kodak Company in which multilayer dry chemistry analytical elements are disclosed. In one embodiment the analytical element contains two layers or zones carried on a support. The zones are initially spaced apart by a spacer means. Under conditions of use, these zones are brought into contact such as by application of suitable compressive force to the upper zone which causes the pressure-deformable spacer means to deform resulting in the upper zone being moved into fluid contact with the lower zone. There is no indication in either reference, however, as to whether the zones are brought into fluid contact after the reaction sequence is completed, although the language in the respective disclosures suggests fluid contact between the zones occurs substantially at the time of sample application.
The need to control the sequential interaction of the test sample with various reagents, while being important in some chemical assays, is of necessity when considering immuno-chemical analysis wherein the antibodies, enzymes and substrates in the reagents must be segregated during storage, introduced into the sample or the reaction mixture-at the proper time and in the proper sequence.
While various proposals have been made with respect to multilayer analysis element utilizing chemical reactions, only a few recent proposals have been made with respect to such multilayer analysis films in which reagents or immunological reaction are incorporated. See, for example, U.S. Pat. No. 4,58,12 assigned to Fuji Photo Film, Co., and the references cited therein. When one attempts to apply immunological reaction techniques to conventional multilayer analysis films, it is difficult to obtain satisfactory analysis data due to problems inherent to immunological analysis as discussed in this reference.
In the aforementioned U.S. Pat. No. 4,587,102 a dry type multilayer analysis element for assaying a concentration of a specific component utilizing a competitive immunological reaction is disclosed. The analysis element contains a detection element comprising a detection layer which receives a labelled complex formed as a result of the competitive immunological reaction, or an optically detectable change dependent upon an amount of the labelled complex of the specific component. Further provided on the detection layer is a reaction layer comprising a fibrous porous medium containing fine particles. While this device attempts to address the problems inherent with immuno-chemical analysis utilizing multilayer analytical elements, it is still a comparatively complex structure requiring many different components and is utilizable only for a limited number of different assay protocols.
There is disclosed in U.S. Pat. No. 4,717,656 assigned to Vertrik Bioteknik AB, a device for chemical analysis which consists essentially of a series of interconnected segments wherein a sample to be tested is contacted with reagents reacting with the sample to form a detectable substance which in turn is detected for a qualitative or quantitative determination. Essentially, the device is a test kit for performing an analysis wherein all chemically active parts which are necessary for carrying out the analysis are built into the device. These chemically active parts are arranged or mounted in such a way that they are connected with the sample and each other by simple folding system. While this device permits the timed, sequential performance of the assay, the physical manipulations of the various segments as required in this device make it totally unusable in an automated analysis system.
U.S. Pat. No. 4,288,228 assigned to the assignee hereof, discloses whole blood analysis and diffusion apparatus therefor. In one embodiment, a precise aliquot is obtained by a carefully controlled cross-diffusion between the porous media via a molecular diffusion switch. The molecular switch achieves accurately timed diffusion of substances from one medium to another, such that an amount (aliquot) of material may be accurately and precisely transferred. The molecular switch is comprised of an impermeable layer which acts as a barrier or isolating means between two porous media. Preferably, this impermeable layer is an immiscible fluid (i.e., gas or liquid) which is easily displaced from between the porous media, and then restored therebetween. Although providing for a timed reaction, this device would not be readily adaptable for use in an automated clinical analyzer.